RESEARCH OBJECTIVES: The long-range objective of this study is to test the validity of an important current hypothesis concerning the etiology of schizophrenia. Mainly derived from pharmacological evidence, this hypothesis suggests that an overproduction of the neurotransmitter dopamine at certain critical sites of the brain as well as a possible imbalance between levels of dopamine and noradrenalin might result in the symptoms of schizophrenia. If so, abnormal or reduced dopamine beta hydroxylase/DBH might well be responsible for the supposed metabolic error. As one approach to studying the foregoing hypothesis, we propose to develope procedures for the isolation of dopamine beta hydroxylase in a homogeneous form from human postmortem brain tissues. First a survey of the regional distribution of the enzyme will be made to identify the most favorable source(s) for its isolation. Work will then be done on bovine brain to adapt and develop optimal procedures for dealing with complex brain tissues and enzyme inhibitors before human brain specimens are used. It is hoped that isolation of human brain DBH will enable development of a specific radioimmunoassay as well as biochemical characterization of the enzyme. Ultimately comparisons will be made between the activities and biochemical characteristics of dopamine beta hydroxylase in the brains of normal and schizophrenic subjects.